Fluid dose, flow and coagulation sensor for medical instrument

ABSTRACT

In combination, an instrument for determining a characteristic of a biological fluid or a control, and a cuvette for holding a sample of the biological fluid or control, the characteristic of which is to be determined. The instrument comprises a radiation-reflective surface, a first source for irradiating the surface, and a first detector for detecting radiation reflected from the surface. The cuvette has two opposed walls substantially transparent to the source radiation and reflected radiation. The first source and first detector are disposed adjacent a first one of the two opposed walls. The radiation reflective surface is disposed adjacent a second of the two opposed walls. A second source is provided for irradiating the surface. The first detector detects radiation from the second source reflected from the surface. The second source is positioned to transmit radiation through the two opposed walls for reflection by the surface and transmission back through the two opposed walls to the first detector to indicate whether a sample has reached a first point in the cuvette.

This is a related application to U.S. Ser. No. 08/114,915, titled ANALOGHEATER CONTROL FOR MEDICAL INSTRUMENT, U.S. Ser. No. 08/114,914, titledPOWER SUPPLY MONITOR AND CONTROL FOR MEDICAL INSTRUMENT, U.S. Ser. No.08/114,896, titled MAGNETIC SYSTEM FOR MEDICAL INSTRUMENT, U.S. Ser. No.08/114,579, titled REAGENT AND METHOD OF ITS USE, and U.S. Ser. No.08/114,897, titled METHOD AND APPARATUS FOR OPERATING A MEDICALINSTRUMENT, all filed on Aug. 31, 1993 and assigned to the sameassignee, the disclosure of which is incorporated herein by reference.U.S. Ser. No. 08/114,915 was abandoned in favor of continuationapplication U.S. Ser. No. 08/554,755 which issued Nov. 10, 1998 as U.S.Pat. No. 5,832,921. U.S. Ser. No. 08/114,914 was abandoned in favor ofcontinuation application U.S. Ser. No. 08/697,019 which issued Aug. 11,1998 as U.S. Pat. No. 5,792,944. U.S. Ser. No. 08/114,896 issued Nov.24, 1998 as U.S. Pat. No. 5,841,023. U.S. Ser. No. 08/114,579 isabandoned. U.S. Ser. No. 08/114,897 issued Jun. 11, 1996 as U.S. Pat.No. 5,526,111. This application is a continuation of U.S. Ser. No.09/724,133, filed Nov. 28, 2000, titled Fluid Dose, Flow and CoagulationSensor for Medical Instrument, assigned to the same assignee as thisapplication. U.S. Ser. No. 09/724,133 issued Jun. 10, 2003 as U.S. Pat.No. 6,575,017. U.S. Ser. No. 09/724,133 is a continuation of U.S. Ser.No. 09/098,708, filed Jun. 17, 1998, titled Fluid Dose, Flow andCoagulation Sensor for Medical Instrument, assigned to the same assigneeas this application. U.S. Ser. No. 09/098,708 issued Feb. 20, 2001 asU.S. Pat. No. 6,189,370. U.S. Ser. No. 09/098,708 is itself acontinuation of U.S. Ser. No. 08/623,872, filed Mar. 29, 1996, titledFluid Dose, Flow and Coagulation Sensor for Medical Instrument, assignedto the same assignee as this application. U.S. Ser. No. 08/623,872issued Aug. 4, 1998 as U.S. Pat. No. 5,789,664. U.S. Ser. No. 08/623,872is itself a continuation of U.S. Ser. No. 08/114,913, filed Aug. 31,1993, titled Fluid Dose, Flow and Coagulation Sensor for MedicalInstrument, assigned to the same assignee as this application. U.S. Ser.No. 08/114,913 issued Jun. 4, 1996 as U.S. Pat. No. 5,522,255. Thebenefit of the filing dates of these prior applications is herebyclaimed.

This invention relates to method and apparatus for determining bloodcoagulation times.

Several methods are known for determining blood coagulation time. Theseinclude laser speckle methods, ultrasonic measurement methods,transmission direct clotting methods, ball and tilted cup directclotting methods, and the methods illustrated in, for example, U.S. Pat.Nos. 4,756,884; 4,849,340; 4,963,498; 5,110,727; and, 5,140,161. Many ofthese prior art methods do not measure blood coagulation times directly,and thus are subject to errors that can enter into indirect measurementprocesses. Many of these methods do not determine whether there is anadequate blood sample, and thus are subject to errors that can enterinto processes which do not determine adequacy of the blood sample. Manyof these methods do not distinguish between blood and control or testsolutions, and thus are subject to errors that can enter into processeswhich do not determine whether a specimen being tested is blood or acontrol or test solution. Many of these methods do not accuratelyascertain the start of a coagulation test, and thus are subject toerrors that can enter into processes which do not ascertain accuratelythe start of a coagulation test. None of these methods combine thespecimen heating function required to obtain accurate coagulation timetest results with a radiation reflector for reflecting test parametersto a radiation detector.

According to the invention, a system is provided for determiningcoagulation time directly by a reflectance technique. According to anillustrative embodiment of the invention, a coagulation testing meteremploys a combination of reflectance sensors and a sample application,start, fill and assay technique to determine coagulation time.

An easy-access, cleanable adapter can be opened by pushing a releasebutton located on the front of the instrument. This provides for easycleaning in the event that contamination occurs during the conduct of atest. The adapter top is hinged toward the back of the adapter and popsup in somewhat the same manner as a car hood when the release button isactuated. The adapter top has a flag that blocks a light path of aninterrupt sensor to indicate when the top is closed in testing position.

A combination reagent heater and reflector includes an aluminum nitrideheater plate which heats the reagent test strip to a controlledtemperature and acts as an optical reflector for a start sensor, anadequate sample sensor, and an assay sensor. A sample sensor which readsthrough the clear bottom of a coagulation time test strip dictates theneed for a heater plate that reflects light.

A sample application icon is a yellow dot that is viewed by the userthrough the clear bottom of the test strip to indicate to the user whereto apply the sample, the coagulation time of which is to be determined.

A sample flow sensor detects that adequate sample has been applied tothe test strip and identifies the type of sample, that is, control orblood, by the flow time signature. The flow time is calculated as thetime difference between actuation of a flow sensor and actuation of astart sensor. This marks the sample type in the coagulation testinginstrument's memory as a control test or a blood test. If the sampletakes longer than an established time stored in read-only memory in theinstrument to flow from the flow sensor to the start sensor, theinstrument stores an indication that the sample volume is insufficient.The flow sensor is a reflective sensor that senses a composite net lossin signal as a result of change of index of refraction, scattering, andabsorption differences between air (no sample applied) and sample (bloodor control).

The start sensor detects when a sample enters the area of a test stripcoated with a coagulation time measurement-assisting reagent. Thisactivates a timer for timing the clotting process. The start sensor alsois a reflective optical sensor that senses a composite net loss insignal as a result of change in index of refraction, scattering, andabsorption differences between air and sample. An LED light sourcedirects light through a clear strip to a heater plate, which reflectslight back through the strip onto a photodetector.

An adequate sample sensor is only activated if a blood sample isdetected within the established time stored in the read-only memory. Theadequate sample sensor detects if the reagent area is covered by thesample. It also prevents the instrument from performing the test if theuser applies a second dose of sample to the strip (double-dosing thestrip), if the second dose is applied more than the established timeafter the first. The sample must flow from the start sensor through afill optical read area of the instrument within the established time, orthe instrument reports insufficient sample. The adequate sample sensoralso is a reflective sensor that senses a composite net loss in signalas a result of change in index of refraction, scattering, and absorptiondifferences between air and sample. An LED light source directs lightthrough the clear strip to the heater plate, which reflects light backthrough the strip onto a photodetector.

An assay sensor outputs a signal that is proportional to the change inheater plate reflectance when modulated by spatial iron particlemovement induced by a 2 Hz alternating electromagnetic field. An LEDlight source directs light through the clear strip to the heater plate,which reflects light back through the strip onto a photodetector. Whenthe sample clots, the iron particles are restricted from moving. Thechange in the reflected light signal decreases. Data collectioncontinues for a predetermined period of time stored in read-only memory.At the end of this predetermined period of time, the collected data isanalyzed to determine the clotting time.

According to one aspect of the invention, an instrument for determiningthe coagulation time of blood, a blood fraction or a control comprises aradiation-reflective surface, a first source for irradiating thesurface, and a first detector for-detecting radiation reflected from thesurface. A cuvette holds a sample of the blood, blood fraction orcontrol the coagulation time of which is to be determined. The cuvettehas two opposed walls substantially transparent to the source radiationand reflected radiation. The first source and first detector aredisposed adjacent a first one of said two opposed walls and theradiation reflective surface is disposed adjacent a second of said twoopposed walls.

According to another aspect of the invention, a method for determiningthe coagulation time of blood, a blood fraction or a control comprisesirradiating a radiation-reflective surface through a cuvette for holdinga sample of the blood, blood fraction or control the coagulation time ofwhich is to be determined using a first radiation source, and detectingradiation reflected from the surface using-a first radiation detector.The cuvette has two opposed walls substantially transparent to thesource radiation and reflected radiation.

Illustratively, according to the invention, the instrument furthercomprises a second source for irradiating the cuvette and a seconddetector for detecting when a sample has been applied to a sampleapplication point in the cuvette. The second detector detects radiationfrom the second radiation source transmitted through one of said twoopposed walls of the cuvette, reflected by the sample and transmittedback through said one wall to the second detector.

Additionally, illustratively according to the invention, a third sourceirradiates the surface. The first detector detects radiation from thethird source reflected from the surface. The third source is positionedto transmit radiation through said two opposed walls for reflection bythe surface and transmission back through said two opposed walls to thefirst detector to indicate that a sample has reached a first point inthe cuvette.

Further, illustratively according to the invention, a fourth sourceirradiates the surface. The first detector detects radiation from thefourth source reflected from the surface. The fourth source ispositioned to transmit radiation through said two opposed walls forreflection by the surface and transmission back through said two opposedwalls to the first detector to indicate that a sample has reached asecond point in the cuvette.

Illustratively, according to the invention, the second point isdownstream in the spread of the sample from the first point and thefirst point is downstream in the spread of the sample from the sampleapplication point.

Additionally, according to the present invention, a heater is providedfor maintaining the blood, blood fraction or control at a desiredtemperature. Means are provided for mounting the heater adjacent thesurface. Means are provided to power the heater. Means are provided formonitoring the surface temperature and for feeding the monitoredtemperature back to the means for providing power to the heater.

Illustratively, the heater comprises an electrically resistive foil. Thesurface comprises a first radiation reflective surface of a plate. Theplate further comprises a second surface opposite the first surfacethereof. Means are provided for mounting the electrically resistive foilto the second surface of the plate.

Further, illustratively according to the invention, the instrumentdetermines coagulation time by combining fluid blood, blood fraction orcontrol with particles which are affected by a magnetic field so thatthe particles become suspended relatively freely in the fluid. Theinstrument further comprises means for generating a time-varyingmagnetic field for causing the particles to be reoriented as themagnetic field varies, with the reorientation changing as the fluidcoagulates owing to the fluid's changing viscosity. Means are providedfor mounting the means for generating the time-varying magnetic fieldadjacent the surface.

Illustratively, the cuvette comprises a region for bearing a code. Theinstrument further comprises one or more fifth radiation sources forirradiating the code bearing region, and one or more third detectors fordetecting the transmission of radiation through the code bearing region.The fifth radiation source or sources and third detector or detectorsare mounted adjacent the code bearing region to detect the code.

Further, illustratively, there are multiple fifth radiation sources anda single third detector. The third detector has an active region whichextends adjacent the code bearing region to detect the transmission ofradiation from all of said fifth radiation sources. Means are providedfor activating the fifth radiation sources in a predetermined sequenceto permit the detection and determination of the code borne by the codebearing region.

The invention may best be understood by referring to the followingdescription and accompanying drawings which illustrate the invention. Inthe drawings:

FIG. 1 illustrates an exploded perspective view of an instrumentconstructed according to the present invention;

FIG. 2 illustrates a fragmentary exploded perspective view of the bottomportion of the instrument illustrated in FIG. 1;

FIG. 3 illustrates a fragmentary exploded perspective view of the topportion of the instrument illustrated in FIG. 1;

FIG. 4 illustrates an exploded perspective view of a detail of FIG. 1;

FIG. 5 illustrates an exploded perspective views of a detail of FIG. 4;

FIG. 6 illustrates an enlarged exploded perspective view of a detail ofFIG. 5;

FIG. 7 a-b illustrate an enlarged, fragmentary, exploded perspectiveview and a fragmentary bottom plan view, respectively, of a detail ofFIG. 5;

FIGS. 8 a–c illustrate a top perspective view, a different topperspective view, and a bottom perspective view, respectively, of adetail of FIG. 5;

FIGS. 9 a–b illustrate an exploded bottom perspective view and anexploded top perspective view, respectively, of a detail of FIG. 5;

FIG. 10 illustrates a top plan view of a detail of FIG. 5;

FIGS. 11 a–d illustrate exploded perspective views of details of FIG. 4;

FIGS. 12 a–b illustrate perspective views from two differentperspectives of a detail of FIG. 4;

FIG. 13 illustrates a block diagram of the electrical system of theinstrument of FIG. 1;

FIG. 14 illustrates a schematic diagram of an electric circuit of theinstrument of FIGS. 1 and 13;

FIGS. 15 a–b illustrate a schematic diagram of an electric circuit ofthe instrument of FIGS. 1 and 13;

FIG. 16 illustrates a reflected light signal and a rectified reflectedlight envelope according to the present invention;

FIGS. 17 a–b illustrate enlarged fragmentary longitudinal sectionalviews taken generally along section lines 17—17 of FIG. 4;

FIG. 18 illustrates a detected light profile according to the presentinvention; and

FIG. 19 illustrates the noise immunization technique of the presentinvention.

The following schematic and block circuit diagram descriptions identifyspecific integrated circuits and other components and in many casesspecific sources for these. Specific terminal and pin names and numbersare generally given in connection with these for the purposes ofcompleteness. It is to be understood that these terminal and pinidentifiers are provided for these specifically identified components.It is to be understood that this does not constitute a representation,nor should any such representation be inferred, that the specificcomponents or sources are the only components available from the same orany other sources capable of performing the necessary functions. It isfurther to be understood that other suitable components available fromthe same or different sources may not use the same terminal/pinidentifiers as those provided in this description.

An instrument 100 for determining the coagulation time of a specimen,whether of blood or of a control, includes a housing 102 comprising ahousing bottom 104 and a housing top 106. Top 106 is provided with abattery door 108 which covers a battery well 110 housing the instrument100's battery power source (not shown). Bottom 104 houses a KyoceraKBS26DA7A piezoelectric beeper 112, and a printed circuit board (PCB)114 onto which are assembled various circuit components which will bedescribed later. An optics assembly 116, a socket 118 for a testparameters electronically erasable programmable read-only memory(EEPROM) key 119 of the type described in U.S. Pat. No. 5,053,199, asocket 120 for serial data communication, and a power supply connector122 for connection of instrument 100 to an external AC/DC adapter (notshown) for operation thereby in lieu of the batteries (not shown) withwhich instrument 100 is typically equipped, are also assembled onto PCB114.

Optics assembly 116 includes a covered 126 strip adapter top assembly132 hinged 128 to a strip adapter bottom assembly 130. Strip adapterbottom assembly 130 includes a magnet assembly 140 held to bottomassembly 130 by a spring clip retainer 142. Magnet assembly 140 includesan 850 turn (#32 A.W.G.) coil 144 wound on a bobbin 146 which ispositioned over the center leg 148 of a 50% nickel/50% iron powderedmetal E-core 150. The end legs 152 of E-core 150 lie outside coil 144. Anine-and-one-half pole per end, flat plate, barium ferrite bias magnet154 is placed over the end of the center leg 148 and is supported on oneend of the bobbin 146. A connector 156 permits electrical connections tobe made-to coil 144.

Strip adapter bottom assembly 130 also includes a sample port housingassembly 160 having a housing 162 within which are mounted a Siemenstype BPW34F photodiode 164 and a Honeywell type SEP8705-003 LED 166.Photodiode 164 senses light generated by LED 166 and reflected from thesample and strip 101 to provide an indication that a sample, be it bloodor control, has been applied to instrument 100 for testing. A connector168 provides for electrical connections to photodiode 164 and LED 166. Aclamp 170 retains LED 166 in housing 162. The angle between the axes ofthe LED 166 and photodiode 164 openings 172, 174, respectively, is about15°.

Strip adapter bottom assembly 130 also includes a heater assembly 180including a heater foil 182 constructed from two Kapton/WA polyamidefilms between which is sandwiched a copper nickel foil trace 183. Athermal fuse 184 and a thermistor 188 are mounted on the side of thefoil 182 opposite the heater trace. Thermal fuse 184 is coupled throughthe foil 182 between one terminal 186 of the heater foil trace and the −HEATER terminal of a heater circuit. Contact is made to the leads ofthermistor 188 from the THermistor + and − leads of the heater circuitthrough a hole 190 in the foil 182. An aluminum nitride heater plate 192having a light reflecting top surface 194 is attached to foil 182 overthe heater pattern area 193 of the heater trace using a thermosettingacrylic adhesive. Electrical connections are made to heater assembly 180through a connector 196.

A transparent polycarbonate window 200 is adhesively attached to aregion 202 of strip adapter bottom assembly housing 203 which is formedwith a series of eight transversely extending slit openings 204-1–204-8,respectively. A transparent polycarbonate window 206 is provided with anopaque glossy black coating 208 over part of its surface and an opaqueglossy yellow coating 210 over part of its surface. The remainder 211 ofwindow 206 remains transparent. Remainder 211 overlies a slit 213 inhousing 203 through which radiation from LED 166 is transmitted to thesample and through which remission from the sample is detected byphotodiode 164. The yellow region 210 visible to the user of instrument100 indicates where the sample, be it blood or control, is to be placedon a transparent disposable strip 101, such as those illustrated anddescribed in U.S. Pat. No. 4,849,340 or the CoaguChek™ coagulationsystem test strip available from Boehringer Mannheim Corporation, 9115Hague Road, Indianapolis, Ind. 46250, when the disposable strip 101 isproperly located in the optics assembly 116. A push-button latch 214including a button 216 biased into locking position by a scissors-shapedcompression spring 218 completes strip adapter bottom assembly 130.

Strip adapter top assembly 132 includes a strip adapter top 222 intowhich is mounted a Centronic type 4500094 bar code reading photodiode224 with an elongated active region exposed through a slot 226 and atransparent polycarbonate window 228 adhesively mounted on the undersideof top 222 to close slot 226. A photosensor bracket 230 capturesphotodiode 224 in position adjacent slot 226. Test strip clampscontaining foam springs 232, useful in pressing test strip 101 againstheater plate 192, have tabs that fit into locating openings providedtherefor in the floor of top 222. Space 235 is provided between clamps232 to accommodate a positioning bracket 236 which is mounted on theunderside of PCB 234 and extends downward therefrom into space 235.Siemens type SFH405-3 START LED 238 and FILL LED 240 are mountedrespectively in front of and behind positioning bracket 236 angled atabout 5° to the normal plane of incidence on PCB 234. A Siemens typeBPW34F photodiode 242 with a daylight filter is mounted on PCB 234inside positioning bracket 236. All three of components 238, 240, 242are exposed downward through openings provided therefor in the bottom ofstrip adapter top 222 of the strip adapter top assembly 132. An Optektype OP290A MAIN assay LED 244 is mounted in an opening 246 providedtherefor in strip adapter top 222 and is held in place by a holdingclamp 248. The leads of LED 244 are connected to PCB 234. The axis ofopening 246 makes an angle of about 45° with the axis of the opening forphotodiode 242 and intersects it.

A pop-up bracket 250 is spring 252-loaded into an opening providedtherefor in a rear end wall 254 of strip adapter top 222 to cause thestrip adapter top assembly 132 to pop up when button 216 is pushed. Aneleven-conductor flat cable 256 and connector 258 make the connectionsbetween the components mounted on PCB 234 and the remaining circuits ofthe PCB 114. Pawl-type catches 260 extend downward from the two forwardcorners of strip adapter top 222. Openings 262 are provided adjacent thefront corners of strip adapter bottom assembly 130 to accommodatecatches 260. Cooperating tongues 263 on button 216 are urged intoengagement with catches 260 by spring 218 when strip adapter bottomassembly 130 and top assembly 132 are closed together. A flag 264 whichextends downward from a side edge of strip adapter top 222 extends intoa slot 266 provided for this purpose in strip adapter bottom assembly130 where flag 264 interrupts a light path from a source to a detectorto indicate that the strip adapter top and bottom assemblies 132, 130,respectively, are closed together.

The electrical circuitry on PCB 114 powers and reads the various sensorsincluded on the coagulation optics circuit 270 on PCB 234. +5V and −5Vare supplied to circuit 270 through terminals 258-5 and 258-1,respectively, of connector 258. Unregulated voltage is supplied toterminal 258-8 of connector 258. Ground for circuit 270 is provided atterminals 258-2, 4 and 7 of connector 258. A 1 μF, 25V capacitor iscoupled across terminals 258-8 and 258-2, 4, 7. The anodes of LEDs 238,240, 244 are all coupled to terminal 258-8. The cathode of LED 238 iscoupled to the START terminal, terminal 258-11, of connector 258. Thecathode of LED 240 is coupled to the FILL terminal, terminal 258-10, ofconnector 258. The cathode of LED 244 is coupled to the MAIN terminal,terminal 258-9, of connector 258.

The anodes of photodiodes 224, 242 are coupled through a 100 KΩ resistor273 to terminal 258-1. The cathode of photodiode 242 is coupled to the −input terminal of an operational amplifier 274. The + input terminal ofoperational amplifier 274 is coupled to the anodes of photodiodes 224,242. The output terminal of operational amplifier 274 is coupled to its− input terminal through a parallel RC feedback circuit including a 560pF capacitor and a 2.21 MΩ, 1%, 50 parts-per-million thermal coefficientresistor. The output terminal of operational amplifier 274 is alsocoupled to the DETect terminal, terminal 258-3, of connector 258.

The cathode of photodiode 224 is coupled to the − input terminal of anoperational amplifier 278. The + input terminal of operational amplifier278 is coupled to the anodes of photodiodes 224, 242. The outputterminal of operational amplifier 278 is coupled to its − input terminalthrough a parallel RC feedback circuit including a 0.001 μF capacitorand a 499 KΩ, 1% resistor. The output terminal of differential amplifier278 is also coupled to the CodeBaR OUTput terminal, terminal 258-6, ofconnector 258. Operational amplifiers 274, 278 illustratively areNational Semiconductor type LPC662IM operational amplifiers.

A +V terminal of a National Semiconductor type LM385M-2.5, 2.5Vreference voltage source 279 is coupled to terminals 258-2, -4 and -7 ofconnector 258. The − terminal of reference voltage source 279 is coupledto the anodes of photodiodes 224, 242, to the + input terminals ofoperational amplifiers 274, 278, and through resistor 273 to the −5Vterminal, 258-1, of connector 258.

The electric circuitry 280 mounted on PCB 114 processes the varioussignals from circuitry 270, as well as others which circuitry 280generates itself or receives from the user of instrument 100, or whichare generated externally to instrument 100. An Intel type N83C51FCeight-bit microcontroller (μC) 284 has data terminals P0.0–P0.7 coupledto DATA lines 0–7, respectively, of an instrument 100 bus 286. μC 284address terminals P2.0–P2.4 and P2.6–P2.7 are coupled to address linesA8–A12 and A14–A15, respectively, of bus 286. The {overscore (ReaD)} and{overscore (WRite)} terminals, P3.7 and P3.6, respectively, of μC 284,are coupled to the {overscore (Read Data)} and {overscore (Write Data)}lines, respectively, of bus 286. An Address Latch Enable terminal of μC284 is coupled to the ALE terminal of a Toshiba type TC11L003AU-1031application specific programmable gate array integrated circuit (ASIC)290. The TIP (transmit) terminal 120-2 of serial data port socket 120 iscoupled through the parallel combination of a 120 pF capacitor and a 220KΩ resistor to ground, and through a 10 KΩ series resistor to theTransmit Data (TXD) terminal P3.1 of μC 284. The RING (receive) terminal120-3 of serial data port socket 120 is coupled through the parallelcombination of a 120 pF capacitor and a 220 KΩ resistor to ground andthrough a 1.2 KΩ series resistor to the Receive Data (RXD) terminal P3.0of μC 284. The GrouND terminal 120-1 of socket 120 is coupled to ground.

The CS terminal 118-1 of ROM key socket 118 is coupled through a Philipstype BZV55C6V2 6.2V Zener diode to ground and directly to a Code ROM ICchip Select OutPut terminal 22 of ASIC 290. The SK terminal, 118-2, ofROM key socket 118 is coupled through a type BZV55C6V2 Zener diode toground and directly to the CLOCK terminal, terminal P1.0, of μC 284. Itis also coupled to the SK terminal of a Samsung type 93C46AK EEPROM 292internal to instrument 100. EEPROM 292 generally contains the meter 100characterizing parameters. The DI and DO terminals, terminals 118-3 and4, of socket 118 are coupled to each other, to ground through aBZV55C6V2 Zener diode, directly to the DI and DO terminals of EEPROM292, and directly to the EEDI/DO terminal P3.5, of μC 284. Terminal118-5 of socket 118 is coupled to ground. Terminal 118-8 of socket 118is coupled to the system +5V supply.

The time base for μC 284 is generated by a 7.3728 MHz crystal which iscoupled across terminals X1–X2 thereof. A 27 pF capacitor is coupledbetween each terminal of the crystal and ground. Terminal P1.5 of μC 284is coupled to a resistive voltage divider including two series 100 KΩresistors in a beeper 112 driver circuit 294. The common terminal of theseries 100 KΩ resistors is coupled to the base of a Siemens type BC848Cdriver transistor 296. The collector of transistor 296 is coupledthrough a 1 KΩ pull-up resistor to +5V and directly to one terminal ofbeeper 112. The emitter of transistor 296 and the other terminal ofbeeper 112 are both coupled to ground. Two type LL4148 diodes clamp thecollector of transistor 296 between ground and +5V.

The data terminals D0–D7 of a Samsung type LH5164-10 8K by 8 staticrandom access memory (SRAM) 300 are coupled to the DATA 0–DATA 7 lines,respectively, of bus 286. The address terminals A0–A12 of SRAM 300 arecoupled via the system bus 286 to the A0–A7 terminals of ASIC 290 andthe A8–A12 terminals of μC 284, respectively. The {overscore (ReaD)} and{overscore (WRite)} terminals of SRAM 300 are coupled via the bus 286 tothe {overscore (ReaD)} and {overscore (WRite)} terminals, respectively,of μC 284. The CE2 terminal of SRAM 300 is coupled to the junction of a390 KΩ resistor and a 0.1 μF capacitor. The other terminal of theresistor is coupled to +5V. The other terminal of the capacitor iscoupled to ground. The CE2 terminal is clamped via a type LL4148 diodeto +5V. The DATA 0–DATA 7 terminals of a Samtron type UC16203GNAR twoline by sixteen character display 302 are coupled to the DATA 0–DATA 7terminals of bus 286. The DISPlay ENable terminal of display 302 iscoupled via bus 286 to the DISPlay ENable terminal of ASIC 290. TheA0–A1 terminals of display 302 are coupled to the A0–A1 terminals,respectively, of bus 286. The GrouND terminal of display 302 is coupledto the system ground and the VDD terminal of display 302 is coupled to+5V. Terminal 3 of display 302 is coupled through a 1 KΩ resistor toground and through an 18 KΩ resistor to +5V. An instrument 100 keypadswitch has its ON/OFF terminal connected to the source of a Samsung typeBSS139 field effect transistor (FET) 303 in instrument 100's powersupply circuit 304. The YES terminal of the switch is coupled to InPutterminal 1 of ASIC 290. The NO terminal of the switch is coupled toInPut terminal 2 of ASIC 290. The YES and NO terminals are also coupledthrough respective 1 MΩ pull-up resistors to +5V.

Battery back-up protection is provided to SRAM 300 by a circuitincluding a 3.3V regulator 306. The V_(in)terminal of regulator 306 iscoupled to the junction of a resistor and a capacitor. The otherterminal of the capacitor is coupled to ground. The other terminal ofthe resistor is coupled to the cathode of a diode, the anode of which iscoupled to +VBAT. The V_(out) terminal of regulator 306 is coupledacross a series resistive voltage divider including a resistor 308 and aresistor 310 to ground. V_(out) is also coupled to the emitter of atransistor 312. The junction of resistors 308, 310 is coupled to thebase of a transistor 314. The emitter of transistor 314 is coupled toground. Its collector is coupled through a series resistor to the baseof transistor 312. The collector of transistor 312 is coupled to theBATtery 1 terminal of a real time clock 316, and to one terminal of acapacitor, the other terminal of which is coupled to ground. The D and Qterminals of IC 316 are coupled to the DATA 0 line of bus 286. The{overscore (CEI)}, {overscore (CEO)}, {overscore (WE)} and {overscore(OE)} terminals of IC 316 are coupled to terminal P2.7(A15) of μC 284,terminal {overscore (CE)} of SRAM 300, the {overscore (Write Data)} lineof bus 286, and the {overscore (Read Data)} line of bus 286,respectively. The VCC OUTPUT terminal of IC 316 is coupled to the VDDterminal of SRAM 300 and through a capacitor to ground. The time basefor IC 316 is generated by a crystal coupled across terminals X1–X2thereof.

The PoWeR INTerrupt, MAIN ConTroL, HeaTeR ON/OFF, A/D OUT, A/D A, A/D B,power SUPPLY ON, SAMPLE ConTroL, and MAGnet 1 ConTroL terminals,terminals P3.2, P3.3, P3.4, P1.1, P1.2, P1.3, P1.4, P1.6 and P1.7,respectively of μC 284, are coupled to the power supply circuit 304, themain LED driver in an LED driver circuit 320, the heater control circuit322, the COMParator OUTput terminal of a Teledyne type TSC500ACOE A/Dconverter IC 324 in the analog section of instrument 100, the A terminalof A/D 324, the B terminal of A/D 324, power supply circuit 304, thesample port circuit 326, and the magnet current control circuit 328.

The InPut 3 terminal of ASIC 290 is coupled to an Omron type EE-SX 1067optical switch 486. The OutPut 10–17 terminals of ASIC 290 are coupledto the bar code LED array driver circuit 330. The OutPut terminals 20,21, 24 and 25 of ASIC 290 are coupled to the setpoint temperaturecontrol of heater driver circuit 322, the LATCH ENABLE terminal of aSignetics type 74HC4351DW eight-to-one analog multiplexer 332 in theanalog section of instrument 100, the fill LED driver in circuit 320,and the start LED driver in circuit 320, respectively. The Address 0–2lines of bus 286 are coupled to the A, B and C terminals, respectively,of multiplexer 332.

Power supply circuit 304 includes an instrument 100 battery connector334 having +VBAT terminal 334-1 and ground terminal connector 334-2 andAC/DC converter power supply connector 122 having +VIN terminals 122-3and 6 connected together and GRouNd terminals 122-1 and 4 connectedtogether. +VBAT is coupled through a series resistor to the gate of FET303. The drain of FET 303 is coupled through two series resistors 336,338 to the base of a transistor 340. The emitter of transistor 340 iscoupled to its base through the series combination of a resistor and adiode, through a diode and 2.0 ampere fuse to +VIN, and through aparallel combination of a transient suppressor diode, a resistor and acapacitor to ground. The junction of resistors 336, 338 is coupledthrough a resistor to the base of a transistor 342. The emitter oftransistor 342 is coupled to the base of transistor 340. The collectorof transistor 342 is coupled through two series resistors to ground. Thecommon terminal of these resistors is coupled to the base of atransistor 346. The emitter of transistor 346 is coupled to ground andits collector is coupled through a pull-up resistor to +5V. Thecollector of transistor 346 is also coupled to InPut terminal 0 of ASIC290.

The emitter of a transistor 350 is coupled to +VBAT. +VBAT is coupledthrough a resistor and a diode in series to the base of transistor 350.The base of transistor 350 is coupled through a diode 351 to the base oftransistor 340. The base of transistor 340 is coupled through a parallelresistance network to the collector of a transistor 352. The emitter oftransistor 352 is coupled to ground. Its base is coupled through aresistor to ground and through a resistor to the collector of atransistor 354. The emitter of transistor 354 is coupled to +5V Analog.The base of transistor 354 is coupled through a resistor to +5 VA. Thebase of transistor 354 is also coupled through a resistor to terminalP1.4 of μC 284. Once the on/off key to meter 100 is depressed uponturn-on, enough time is given for the +5V supply to come up and the μC284 to reset itself (once +5V supply has been applied to its V_(cc) pin)and then to have terminal P1.4 of μC 284 latch the system +5V supply on.This terminal is also used to shut the system down in an orderlyfashion. VUNREGulated appears at the collector of transistor 350 and atthe cathode of a diode 356, the anode of which is coupled to thecollector of transistor 340.

Regulation is initiated by battery voltage +VBAT on the gate of FET 303.If the battery is in backward, or is below minimum regulation level andno AC/DC adapter is connected to instrument 100, or is missing and noAC/DC adapter is connected to instrument 100, the instrument 100 cannotbe turned on. If the battery is installed properly and is above minimumregulation level, regulation is established at the base of transistor340 and, through diode 351, at the base of transistor 350. Regulation isalso signalled through transistors 342 and 346 to the ON/OFF INDicatorInPut terminal 0 of ASIC 290. If the battery voltage +VBAT is greaterthan +VIN, diode 356 decouples the AC/DC adapter input circuity,including transistor 340 and its associated regulating circuitry fromVUNREGulated so that the battery does not power that circuitry.

VUNREGulated is supplied to the VIN terminal of a +5V regulator IC 360.VUNREGulated is also supplied to a series voltage divider including aresistor 362 and a resistor 364. The common terminal of resistors 362,364 is coupled to the INput terminal of a voltage detector IC 366. TheERROR output terminal of IC 366 is coupled through a resistor toVUNREGulated and through a resistor to the base of a transistor 368. Thecollector of transistor 368 is coupled through a load resistor toVUNREGulated and is coupled directly to the SHUTDOWN terminal of +5Vregulator IC 360. If the supply voltage is low, IC 366 will preventinstrument 100 from being turned on. Regulated +5V for the digitalcircuitry of instrument 100 appears at the VOUT terminal of +5Vregulator IC 360. The SENSE terminal of IC 360 is coupled to +5V. TheERROR terminal of IC 360 is coupled through a pull up resistor to +5V.The ERROR terminal is also coupled to the PoWeRINTerrupt terminal, P3.2,of μC 284. The error terminal's main function is to warn the μC 284 thatthe system power is approaching an unregulated condition. By warning μC284 of such condition, μC 284 can power down the system in an orderlyfashion prior to any soft failures occurring. A capacitor across VOUTand GrouND of IC 360 is decoupled by a resistor from a tantalumcapacitor across the +5 VAnalog supply to analog ground. The voltageacross the VOUT output terminal to ground is fed back through a diodeand resistor in series to the base of transistor 368. The VOUT outputterminal of IC 360 is also coupled to the V+ terminal of a +5V-to-−5Vconverter 369. A tantalum capacitor is coupled across the CAP+ and CAP−terminals of converter 369. −5 VDC for circuits requiring it appearsacross the VOUT terminal of converter 369 to ground. The instrument100's analog and digital grounds are tied together here. A +V terminalof a 2.5V reference voltage source 370 is coupled through a resistor to+5 VAnalog. 2.5 VREFerence is established across the +V terminal ofsource 370 and ground.

Turning now to the LED driver circuitry 320 for the optical headassembly 116, the start LED control OutPut terminal 25 of ASIC 290 iscoupled through a type LL4148 diode to the − input terminal of a Samsungtype LM324A operational amplifier 374. The + input terminal ofoperational amplifier 374 is coupled to VREF. The output terminal ofoperational amplifier 374 is coupled to the base of a Philips typePXT4401 transistor 376. The collector of transistor 376 is coupled tothe START LED terminal, terminal 258-11, of connector 258. The emitterof transistor 376 is coupled to ground through a 100Ω resistor, whichlimits the current through the start LED at a constant current, andthrough a 100 KΩ feedback resistor to the − input terminal ofoperational amplifier 374.

The FILLConTroL terminal, Output terminal 24, of ASIC 290 is coupledthrough a type LL4148 diode to the − input terminal of a type LM324Aoperational amplifier 378. The + input terminal of operational amplifier378 is coupled to VREF. The output terminal of operational amplifier 378is coupled to the base of a type PXT4401 NPN transistor 380, thecollector of which is coupled to the FILL LED terminal, terminal 258-10,of connector 258. The emitter of transistor 380 is coupled through aparallel resistor network, the effective resistance of which is 50 Ω, toground, which limits the current through the fill LED at a constantcurrent, and through a 100 KΩ feedback resistor to the − input terminalof operational amplifier 378.

The MAIN ConTroL terminal, P3.3, of μC 284 is coupled through a typeLL4148 diode to the − input terminal of a type LM324A operationalamplifier 382. The + input terminal of operational amplifier 382 iscoupled to VREF. The output terminal of operational amplifier 382 iscoupled to the base of a Philips type PXTA14 Darlington-coupledtransistor pair 384. The collectors of transistors 384 are coupled tothe MAIN assay LED terminal, 258-9, of connector 258. The emitter oftransistors 384 is coupled through a 100 Ω 1%, 25 parts-per-milliontemperature coefficient resistor to ground, which limits the currentthrough the main LED at a constant current, and through a 100 KΩresistor, to the − input terminal of operational amplifier 382.

The sensed bar code of the disposable test strip 101 which is being usedin a particular test comes in to circuit 320 serially on the CodeBaRterminal, 258-6, of connector 258. It is coupled directly to analoginput terminal X5 of multiplexer 332. The START, FILL and MAIN assayDETect signals indicating that an adequate volume sample droplet hasbeen placed over yellow area 210 on a test strip 101, and its rawcoagulation results data, are provided from terminal 258-3 of connector258 to the + input terminals of two type LM324A operational amplifiers386, 388. Operational amplifier 386 is configured as a unity gain bufferand its output terminal is coupled to the DC input terminal X1 ofmultiplexer 332. Operational amplifier 388 is also configured as a unitygain buffer and its output terminal is capacitively coupled through a0.1 μF capacitor and two series 100 KΩ resistors 390, 392 to a + inputterminal of a type LPC662IM operational amplifier 394. The outputterminal of operational amplifier 388 is also coupled to ground throughan RC parallel combination of a 1.5 MΩ resistor and 0.0033 pF capacitor.The + terminal of operational amplifier 394 is coupled to ground througha 0.056 μF capacitor. The output terminal of operational amplifier 394is coupled through a 2 MΩ, 1% feedback resistor to its − input terminal.Its − input terminal is coupled to ground through a 221 KΩ, 1% resistor.The output terminal of operational amplifier 394 is also coupled throughseries 100 KΩ, 1% and 20 KΩ, 1% resistors 396, 398, respectively, toground. The common terminal of resistors 396, 398 is coupled through a0.056 μF capacitor to the common terminal of resistors 390, 392.

The signal at the output terminal of operational amplifier 394 isdirectly coupled to the X0 input terminal, AC1, of multiplexer 332. Thatsignal is also coupled to the + input terminal of a type LPC662IMoperational amplifier 400. The signal at the output terminal ofoperational amplifier 400 is directly coupled to the X2 input terminal,AC2, of multiplexer 332. The output terminal of operational amplifier400 is also coupled through a 3 MΩ, 5% resistor to the − input terminalthereof. The − input terminal of operational amplifier 400 is coupledthrough a 1 MΩ, 5% resistor to ground.

VUNREGulated is coupled through a series voltage divider including aresistor 402 and a resistor 404 to ground. The common terminal ofresistors 402, 404 is coupled directly to the analog BATTery voltageinput terminal X4 of multiplexer 332. +5 VA is coupled to the VDD inputterminal of a temperature sensor 406. The VOUT terminal of sensor 406 iscoupled directly to the analog VTEMP voltage input terminal, X6, ofmultiplexer 332 and through a pull-up resistor to +5 VA.

The heater control circuit 322 includes two series resistors 410, 412coupled between the HeaTeR ON/OFF terminal of μC 284 and ground. Thecommon terminal of resistors 410, 412 is coupled to the base of atransistor 414, the collector of which is coupled through two seriesresistors 416, 418 to +5 VA, and the emitter of which is coupled toground. The common terminal of resistors 416, 418 is coupled to the baseof a transistor 420, the emitter of which is coupled to +5 VA, and thecollector of which is coupled through a series resistor 422 andcapacitor 424 to ground. The common terminal of resistor 422 andcapacitor 424 is coupled to the − input terminal of an operationalamplifier 426.

+5 VA is coupled through a series resistor, a potentiometer 428 and aresistor to ground. The movable contact of potentiometer 428 is coupledto the − input terminal of operational amplifier 426. The potentiometerenables the heater plate 192 to achieve about 39° C. +5 VA is coupledthrough a series resistor 430 and capacitor 432 to ground. The commonterminal of resistor 430 and capacitor 432 is coupled to theTHermistor + terminal, 196-3, of connector 196, and to the + inputterminal of operational amplifier 426. The + input terminal ofoperational amplifier 426 is coupled through the series combination of adiode and a resistor to ground. The junction of the resistor and diodeis coupled to the base of a transistor 434, the emitter of which iscoupled to ground. The output terminal of operational amplifier 426 iscoupled through a resistor to its − input terminal and through theseries combination of a diode and a resistor to the collector oftransistor 434.

The SETPoinT 2 terminal, OutPut terminal 20, of ASIC 290, is coupledthrough series resistors 436, 438 to +5 VA. The ASIC 290 providescontrol of the heater plate 192 temperature at two different setpoints,39° C. and 44° C. The second setpoint is set high to permit the heaterplate 192 to attain 44° C. temperature, thereby permitting more rapidwarming of samples to 39° C. The common terminal of resistors 436, 438is coupled to the base of a transistor 440, the emitter of which iscoupled to +5 VA and the collector of which is coupled through aresistor to the − input terminal of operational amplifier 426. A seriesresistive voltage divider including a resistor 442 and a resistor 444 iscoupled between the output terminal of operational amplifier 426 andground. The common terminal of resistors 442, 444 is coupled to ananalog input terminal X3 of multiplexer 332. Heater control circuit 322operating status is thus multiplexed into μC 284. Additionally, heatercontrol status, as reflected by the voltage at the collector oftransistor 434, controls the flow of current through the heater foil182. This is accomplished through a transistor 446, the base of which iscoupled to the collector of transistor 434 and the collector of which iscoupled to the − HEATER terminal, 196-2, of connector 196. The + HEATERterminal, 196-1, of connector 196 is coupled to + VUNREGulated. Theemitter of transistor 446 is coupled through a parallel resistancenetwork to ground. The base of transistor 446 is also coupled throughtwo series diodes to ground, which limits the current through the heaterfoil to approximately 0.4 A. The − THermistor terminal, 196-4, ofconnector 196 is coupled to ground.

Terminal P1.6 of μC 284 is coupled through a type LL4148 diode to the −input terminal of a type LM324A operational amplifier 450 in the sampleport circuit 326. The + input terminal of operational amplifier 450 iscoupled to VREF. The output terminal of operational amplifier 450 iscoupled to the base of a type BC848C NPN transistor 452, the emitter ofwhich is coupled through a 100 KΩ feedback resistor to the − inputterminal of operational amplifier 450 and to ground through 60Ωresistance, which limits the current through the sample port LED at aconstant current. The collector of transistor 452 is coupled to terminal168-1 of the sample port connector 168. +5 VA is coupled to terminal168-2, the VDD terminal, of connector 168. VUNREGulated is coupled toterminal 168-5 of connector 168. The SAMPle IN terminal, 168-4, ofconnector 168 is coupled to ground through a 20 KΩ, 1% resistor andthrough a 0.001 μF capacitor to the − input terminal of a, type LPC662IMoperational amplifier 456. The + input terminal of operational amplifier456 is coupled to ground. The output terminal of operational amplifier456 is coupled through a parallel RC feedback circuit including a 200KΩ, 1% resistor and a 39 pF capacitor to its − input terminal. Theoutput terminal of operational amplifier 456 is coupled through a 0.0047μF capacitor to the + input terminal of a type LPC662IM operationalamplifier 458. The + input terminal of operational amplifier 458 iscoupled to ground through a 15 KΩ, 1% resistor.

The − input terminal of operational amplifier 458 is coupled to groundthrough a 20 KΩ, 1% resistor. The output terminal of operationalamplifier 458 is coupled to the cathode of a type LL4148 diode, theanode of which is coupled through a 100 KΩ, 1% resistor to the − inputterminal of operational amplifier 458. The output terminal ofoperational amplifier 458 is also coupled to the anode of a type LL4148diode 460, the cathode of which is coupled through a 1 MΩ, 1% resistor462 to the − input terminal of operational amplifier 458. This providesa hysteresis-type configuration which has different gains depending uponwhether the voltage at the + input terminal of operational amplifier 458is greater than or less than the voltage at the − input terminalthereof. The common terminal of diode 460 and resistor 462 is coupledthrough the series combination of a 1 KΩ, 1% resistor 464 and a 0.047 μFcapacitor 466 to ground. The common terminal of resistor 464 andcapacitor 466 is coupled to the SAMPle DETect input terminal, X7, ofmultiplexer 332.

Terminal P1.7 of μC 284 is coupled through two series resistors in themagnet control circuit 328 to ground. The common terminal of theseresistors is coupled to the base of a transistor 470, the emitter ofwhich is coupled to ground. The collector of transistor 470 is coupledthrough series resistors to +5 VA. The common terminal of theseresistors is coupled to the base of a transistor 471, the emitter ofwhich is coupled to +5 VA and the collector of which is coupled to the −input terminal of an operational amplifier 472. The series combinationof a resistor 474 and a resistor 476 is coupled between VREF and ground.A capacitor is coupled across resistor 476. The common terminal ofresistors 474 and 476 is coupled to the + input terminal of operationalamplifier 472.

The output terminal of operational amplifier 472 is coupled to the baseof a magnet coil 144-driver transistor 478. The emitter of transistor478 is coupled through a resistor to ground, which limits the currentthrough the magnet coil at a constant current, and through a feedbackresistor to the − input terminal of operational amplifier 472. Acapacitor is coupled between the − input terminal of operationalamplifier 472 and ground. The collector of transistor 478 is coupled toterminal 156-3 of connector 156. Terminal 156-1 of connector 156 iscoupled to VUNREGulated., Coil 144 is coupled across connectors 156-1and 156-3. The series combination of a resistor and a capacitor is alsocoupled across connectors 156-1 and 156-3. A flyback diode is alsocoupled across terminals 156-1 and 156-3.

The bar code LED driver circuit 330 which is associated with photodiode224 includes eight Stanley type BR1102W bar code-illuminating LEDs484-1–484-8. The anode of LED 484-1 is coupled to +5V and its cathode iscoupled to the Anode terminal of optical switch 486. Optical switch 486provides the source and detector for flag 264 to indicate when the stripadapter top and bottom assemblies 130, 132 are closed together. Thecollector terminal, C, of optical switch 486 is coupled to InPutterminal 3 of ASIC 290, and through a 100 KΩ load resistor to +5V. Thecathode terminal, K, of optical switch 486 is coupled through a 120Ωload resistor to the collector of a type BC848C NPN transistor 490-1,the emitter of which is coupled to ground and the base of which iscoupled through a 10 KΩ resistor to OutPut terminal 17 of ASIC 290. Theanodes of the remaining LEDs 484-2–484-8 are coupled through a common60Ω load resistance to +5V. The cathodes of LEDs 484-2–484-8 are coupledto the collectors of type BC848C NPN transistors 490-2–490-8,respectively. The emitters of transistor 490-2–490-8 are coupled toground. The bases of transistor 490-2–490-8 are coupled throughrespective 10 KΩ resistors to OutPut terminals 16–10, respectively, ofASIC 290.

LEDs 484-1–484-8 are mounted on PCB 114 and emit light throughrespective slit openings 204-1–204-8, respectively. LED's 484-1–484-8are sequentially energized through transistors 490-1–490-8,respectively. The presence or absence of a bar code in region 492 of aparticular test strip 101 placed in instrument 100 is sensed bytransmission of light from a respective LED 484-1–484-8 by conduction ofphotodiode 224. This identifies certain test strip 101 lot-specificparameters for instrument 100.

In operation, a sample 514 is deposited in the test strip 101 samplewell 494 over location 210. Radiation from LED 164, which is strobed at0.25 sec. intervals, detected by photodiode 166 establishes the dosingof strip 101. START LED 238 is strobed at 50 msec. intervals until thearrival of the sample 514 at the region of strip 101 over START LED 238is established by the radiation from START LED 238 detected byphotodiode 242. The flow time of the sample 514 between the sampleapplication point at well 494 and the detection of the arrival of thesample 514 over the START LED 238 establishes the sample 514 as blood ora control. The control solutions, being less viscous, flow between thesetwo locations more rapidly, and this is detected by the instrument 100.The minimum flow time that the instrument 100 will interpret as bloodand/or the maximum flow time that the instrument 100 will interpret ascontrol can be varied from strip lot to strip lot by changing (a)parameter(s) in the user-insertable EEPROM key 119. This relieves theuser from the need to indicate to the instrument 100 or otherwise recordwhen a quality control check is being conducted.

After photodiode 242 has detected the arrival of the sample 514 over theSTART LED 238, the START LED 238 is deenergized and the FILL LED 240 isenergized. The next decrease in radiation detected by photodiode 242indicates the arrival of the sample 514 over the FILL region of thestrip 101. The elapsed time between detection by photodiode 242 ofarrival of the sample 514 over START LED 238 and detection by photodiode242 of arrival of the sample 514 over FILL LED 240 is used by theinstrument 100 to determine whether the volume of the sample 514 whichwas applied is adequate to conduct a coagulation test. If the instrument100 determines that the applied sample 514 volume was inadequate toconduct a test, the instrument 100 provides an error message and returnsto its ready state. If the instrument 100 determines that the appliedsample 514 volume was sufficient to conduct a coagulation time testreliably, FILL LED 240 is deenergized and MAIN assay LED 244 isenergized. Electromagnet 140 is also energized and monitoring byphotodiode 242 of MAIN assay LED 244 radiation begins. Magnet assembly140, when driven by magnet current control circuit 328, stirsferromagnetic particles from the test strip 101 borne by the sample 514,be it blood or control. The particles reorient themselves along thecombined lines of force of magnet assembly 140 and bias magnet 154 andprovide a modulated light transmission profile of the sample. Thistransmission profile, illustrated in FIG. 16 at 500, is detected byphotodiode 242 and is multiplexed (DETect-AC1-DC) via multiplexer 332and A/D 324 into μC 284. Coagulation of the sample causes the reductionin the modulation in this transmission profile as described in U.S. Pat.Nos. 4,849,340 and 5,110,727. Waveform 500 is rectified and the envelope502 of the rectified waveform 500 is formed.

To reduce the likelihood of double dosing the strip 101, the ratio ofSTART to FILL time-to-sample application to START time is formed. Thisratio is compared to a parameter provided from key 119. The ratio mustbe less than the parameter. Otherwise the instrument 100 will concludethat the strip 101 has been double dosed and will generate an errormessage. Double dosing is to be avoided because it can refluidize theferromagnetic particles, producing an erroneous coagulation timereading.

FIGS. 17 a–b are much-enlarged fragmentary longitudinal sectional viewsof a strip 101 taken along section lines 17—17 of FIG. 4. Generally, inthe absence of liquid blood, a blood fraction or control (FIG. 17 a),the indices of refraction of the strip bottom 506 and top 508 and theair-filled sample volume 510 between them are such that the level oflight from LED 164 returning to photodiode 166 is relatively higher.This is illustrated at region 512 of FIG. 18. A liquid sample 514, be itblood, a blood fraction or a control, is deposited into the sample well494 of strip 101 and migrates into region 510 of strip 101 over region211 of instrument 100. Owing generally to the matching of the stripbottom 506's, top 508's and liquid 514's indices of refraction andabsorption in the case of clear liquids, and generally to absorption andscattering effects in the case of whole blood, a relatively lower lightlevel is detected by photodiode 166 as illustrated at region 522 in FIG.18 when a liquid is present on strip 101 adjacent region 211. Thisoptical detection scheme permits a clear control to be used.

FIG. 19 illustrates two waveforms useful in understanding the startnoise immunization technique employed in an instrument according to thepresent invention. It has been experimentally determined that, unlessprovisions are made in instrument 100 to prevent it, instrument 100 canbe falsely triggered by negative-going noise spikes 526 that aregenerated during application of a sample to a test strip 101. Suchspikes 526 are caused when the user accidentally taps or moves the strip101 from side to side or in and out of the optics assembly 116 duringsample application. Such negative-going spikes 526 can be greater thanthe instrument 100's −60 mV starting threshold, but are typicallyshorter in duration than the negative-going start signal 528 and arepreceded or followed immediately by positive-going spikes 530. This isin contrast to the actual liquid sample signal 528 which is onlynegative-going. This difference is used to discriminate effectivelybetween signal 528 and noise 526, 530. The instrument 100's STARTalgorithm discriminates between short (noise) 526, 530 and long (startsignal) 528 duration signals using negative trend, rate of signal changeand negative threshold criteria. The flow of the START algorithmincludes the following illustrative characteristics: three consecutivedata points sampled 50 msec apart must be negative relative to areference and have rates of signal change more negative than −7.3 mV/50msec (−30 counts of the A/D converted input signal at 0.243 mV/count)with an absolute signal change more negative than the −60 mV (−246counts) instrument 100 start threshold. The parameters stored in theEEPROM 119 then would include a signal delta of −30 counts and a startthreshold of −246 counts.

1. In combination, an instrument for determining a characteristic of abiological fluid or a control comprising a radiation-reflective surface,a first source for irradiating the surface, and a first detector fordetecting radiation reflected from the surface, and a cuvette forholding a sample of the biological fluid or control the characteristicof which is to be determined, the cuvette having two opposed wallssubstantially transparent to the source radiation and reflectedradiation, the first source and first detector being disposed adjacent afirst one of said two opposed walls and the radiation reflective surfacebeing disposed adjacent a second of said two opposed walls, a secondsource for irradiating the surface, the first detector detectingradiation from the second source reflected from the surface, the secondsource positioned to transmit radiation through said two opposed wallsfor reflection by the surface and transmission back through said twoopposed walls to the first detector to indicate whether a sample hasreached a first point in the cuvette, a third source for irradiating thesurface, the first detector detecting radiation from the third sourcereflected from the surface, the third source positioned to transmitradiation through said two opposed walls for reflection by the surfaceand transmission back through said two opposed walls to the firstdetector to indicate whether a sample has reached a second point in thecuvette, the cuvette comprising a region for bearing a code, theinstrument further comprising one or more fourth radiation sources forirradiating the code bearing region, one or more second detectors fordetecting the transmission of radiation through the code bearing region,the fourth radiation source or sources and second detector or detectorsmounted adjacent the code bearing region to detect the code, a heaterfor maintaining the biological fluid or control at a desiredtemperature, means for mounting the heater adjacent the surface, meansfor providing power to the heater and means for monitoring the surfacetemperature and for feeding the monitored temperature back to the meansfor providing power to the heater, the heater comprising an electricallyresistive foil, the surface comprising a first radiation reflectivesurface of a tile, the tile further comprising a second surface oppositethe first surface thereof, and means for mounting the electricallyresistive foil to the second surface of the tile.
 2. In combination, aninstrument for determining a characteristic of a biological fluid or acontrol comprising a radiation-reflective surface, a first source forirradiating the surface, and a first detector for detecting radiationreflected from the surface, and a cuvette for holding a sample of thebiological fluid or control the characteristic of which is to bedetermined, the cuvette having two opposed walls substantiallytransparent to the source radiation and reflected radiation, the firstsource and first detector being disposed adjacent a first one of saidtwo opposed walls and the radiation reflective surface being disposedadjacent a second of said two opposed walls, a second source forirradiating the surface, the first detector detecting radiation from thesecond source reflected from the surface, the second source positionedto transmit radiation through said two opposed walls for reflection bythe surface and transmission back through said two opposed walls to thefirst detector to indicate whether a sample has reached a first point inthe cuvette, a third source for irradiating the surface, the firstdetector detecting radiation from the third source reflected from thesurface, the third source positioned to transmit radiation through saidtwo opposed walls for reflection by the surface and transmission backthrough said two opposed walls to the first detector to indicate whethera sample has reached a second point downstream in the spread of thesample from the first point in the cuvette, the cuvette comprising aregion for bearing a code, the instrument further comprising one or morefourth radiation sources for irradiating the code bearing region, one ormore second detectors for detecting the transmission of radiationthrough the code bearing region, the fourth radiation source or sourcesand second detector or detectors mounted adjacent the code bearingregion to detect the code, a heater for maintaining the biological fluidor control at a desired temperature, means for mounting the heateradjacent the surface, means for providing power to the heater and meansfor monitoring the surface temperature and for feeding the monitoredtemperature back to the means for providing power to the heater, theheater comprising an electrically resistive foil, the surface comprisinga first radiation reflective surface of a tile, the tile furthercomprising a second surface opposite the first surface thereof, andmeans for mounting the electrically resistive foil to the second surfaceof the tile.